Short-lag spatial coherence beamforming of photoacoustic images for enhanced visualization of prostate brachytherapy seeds

Prostate brachytherapy, administered by implanting tiny radioactive seeds to treat prostate cancer, currently relies on transrectal ultrasound imaging for intraoperative visualization of the metallic seeds. Photoacoustic (PA) imaging has been suggested as a feasible alternative to ultrasound imaging due to its superior sensitivity to metal surrounded by tissue. However, PA images suffer from poor contrast when seeds are distant from the light source. We propose a transperineal light delivery method and investigate the application of a short-lag spatial coherence (SLSC) beamformer to enhance low-contrast photoacoustic signals that are distant from this type of light source. Performance is compared to a conventional delay-and-sum beamformer. A pure gelatin phantom was implanted with black ink-coated brachytherapy seeds and the mean contrast was improved by 3–25 dB with the SLSC beamformer for fiber-seed distances ranging 0.6–6.3 cm, when approximately 10% of the receive aperture elements were included in the short-lag sum. For fiber-seed distances greater than 3–4 cm, the mean contrast-to-noise ratio (CNR) was approximately doubled with the SLSC beamformer, while mean signal-to-noise ratios (SNR) were mostly similar with both beamformers. Lateral resolution was decreased by 2 mm, but improved with larger short-lag values at the expense of poorer CNR and SNR. Similar contrast and CNR improvements were achieved with an uncoated brachytherapy seed implanted in ex vivo tissue. Results indicate that the SLSC beamformer has potential to enhance the visualization of prostate brachytherapy seeds that are distant from the light source.OCIS codes: (170.5120) Photoacoustic imaging, (100.0100) Image processing, (100.3010) Image reconstruction techniques, (030.1640) Coherence, (170.1650) Coherence imaging, (170.7230) Urology     

经直肠多模态超声影像评分系统诊断前列腺癌的临床研究

目的建立前列腺癌多模态超声影像评分系统,并评价该评分系统对前列腺癌的诊断价值。 方法选取2016年5月至2017年12月在解放军总医院行超声引导下穿刺活检和（或）手术切除的86例可疑前列腺癌患者,术前对前列腺行经直肠常规超声、剪切波弹性成像、超声造影检查,分析三种模态超声影像特征,并与手术或穿刺病理进行对照。总结前列腺癌经直肠多模态超声影像特征,建立评分系统,并评价该系统对前列腺癌的诊断价值。 结果前列腺癌常规超声表现为低回声、边界不清、形态不规则、内外腺分界不清、包膜侵犯、血流信号丰富且为中心血流;剪切波弹性成像表现为非对称分布,前列腺癌病灶平均弹性模量高于良性病灶［（94.7±44.2）kPa vs（60.8±26.0）kPa］,差异有统计学意义（t=-3.578,P=0.001）;超声造影表现为快速高增强,分布不均匀（低增强区伴点状血管结构,点状、片状或结节状高增强）,内外腺分界不清,包膜或直肠壁侵犯。常规超声、超声造影、弹性成像有1项阳性即诊断为前列腺癌,其敏感度、阴性预测值和准确性分别为98.0%、96.7%和89.5%;三者均为阳性诊断为前列腺癌,其特异度和阳性预测值分别为97.3%和97.1%。 结论经直肠多模态超声影像评分系统可提高超声对前列腺癌的诊断价值。     

Transrectal ultrasonography for the detection and staging of carcinoma of the prostate

Transrectal ultrasonography (TRUS) has become the most frequently used imaging modality for the prostate. The internal architecture of the prostate is readily detailed by TRUS, and the procedure allows an accurate measurement of prostate size. Carcinoma of the prostate has a characteristic hypoechoic pattern which is sometimes distinct from the normal echo pattern of the peripheral portion of the prostate. TRUS does not have sufficient sensitivity and specificity to support its use for routine screening for prostate cancer. In men with an abnormality of either digital rectal palpation of the prostate or serum prostate specific antigen, TRUS is useful for directing prostate biopsy. Transrectal core biopsies are obtained under ultrasound direction, and precise placement of the biopsy needles can be accomplished using TRUS. © 1996 John Wiley & Sons, Inc.     

Multiparametric Ultrasound for Targeting Prostate Cancer: Combining ARFI,SWEI, QUS and B-Mode

Diagnosing prostate cancer through standard transrectal ultrasound (TRUS)-guided biopsy is challenging because of the sensitivity and specificity limitations of B-mode imaging. We used a linear support vector machine (SVM) to combine standard TRUS imaging data with acoustic radiation force impulse (ARFI) imaging data, shear wave elasticity imaging (SWEI) data and quantitative ultrasound (QUS) midband fit data to enhance lesion contrast into a synthesized multiparametric ultrasound volume. This SVM was trained and validated using a subset of 20 patients and tested on a second subset of 10 patients. Multiparametric US led to a statistically significant improvements in contrast, contrast-to-noise ratio (CNR) and generalized CNR (gCNR) when compared with standard TRUS B-mode and SWEI; in contrast and CNR when compared with MF; and in CNR when compared with ARFI. ARFI, MF and SWEI also outperformed TRUS B-mode in contrast, with MF outperforming B-mode in CNR and gCNR as well. ARFI, although only yielding statistically significant differences in contrast compared with TRUS B-mode, captured critical qualitative features for lesion identification. Multiparametric US enhanced lesion visibility metrics and is a promising technique for targeted TRUS-guided prostate biopsy in the future.     

Contrast-Specific Spherical Lesion Phantoms and Ancillary Analysis Software for the Objective Evaluation of Transrectal Ultrasound System Contrast Detectability

Brachytherapy is an efficacious treatment option because of its benefits for patient recovery, dose localization and conformity, but these favorable outcomes can be ensured only if the transrectal ultrasound (TRUS) system is optimized for the specific application of ultrasound-guided prostate brachytherapy. The ability to delineate the prostate from surrounding tissue during TRUS-guided prostate brachytherapy is vital for treatment planning, and consequently, so is the contrast resolution. This study describes the development of task-specific contrast-detail phantoms with clinically relevant contrast and spherical target sizes for contrast-detail performance evaluation of TRUS systems used in the brachytherapy procedure. The procedure for objective assessment of the contrast detectability of the TRUS systems is also described; a program was developed in MATLAB (R2017a, The MathWorks, Natick, MA, USA) to quantitatively analyze image quality in terms of the lesion signal-to-noise ratio (LSNR) and validated with representative control test images. The LSNR of the Hitachi EUB-7500A (2013, Hitachi, Ltd, Tokyo, Japan) TRUS system was measured on sagittal and transverse TRUS images of the contrast-detail phantoms described in this work. Results revealed the efficacy of the device as an image quality evaluation tool and the impact of the size, depth and relative contrast of the targets to the surrounding tissue on the contrast detectability of a TRUS system for both transducer arrays. The MATLAB program objectively measured the contrast detectability of the TRUS system and has the potential to determine optimized imaging parameters that could be designed as part of standardization of the imaging protocol used in TRUS-guided prostate brachytherapy for prostate cancer.     

Quantifying Gleason scores with photoacoustic spectral analysis: feasibility study with human tissues

Gleason score is a highly prognostic factor for prostate cancer describing the microscopic architecture of the tumor tissue. The standard procedure for evaluating Gleason scores, namely biopsy, is to remove prostate tissue for observation under microscope. Currently, biopsies are guided by transrectal ultrasound (TRUS). Due to the low sensitivity of TRUS to prostate cancer (PCa), non-guided and saturated biopsies are frequently employed, unavoidably causing pain, damage to the normal prostate tissues and other complications. More importantly, due to the limited number of biopsy cores, current procedure could either miss early stage small tumors or undersample aggressive cancers. Photoacoustic (PA) measurement has the unique capability of evaluating tissue microscopic architecture information at ultrasonic resolution. By frequency domain analysis of the broadband PA signal, namely PA spectral analysis (PASA), the microscopic architecture within the assessed tissue can be quantified. This study investigates the feasibility of evaluating Gleason scores by PASA. Simulations with the classic Gleason patterns and experiment measurements from human PCa tissues have demonstrated strong correlation between the PASA parameters and the Gleason scores.OCIS codes: (170.6510) Spectroscopy, tissue diagnostics; (120.3890) Medical optics instrumentation; (110.5125) Photoacoustics; (170.6935) Tissue characterization     

Development and Preliminary Evaluation of an Anthropomorphic Trans-rectal Ultrasound Prostate Brachytherapy Training Phantom

The quality of the trans-rectal ultrasound (TRUS) image, and thus seed placement during the prostate brachytherapy (PBT) procedure, relies on the user's technical and clinical competency. Simulation-based medical education can provide a structured approach for the acquisition of clinical competencies, but the efficacy of the training relies on the fidelity of the training simulators. In this work, the design, development and preliminary evaluation of an anthropomorphic training phantom for TRUS PBT is described. TRUS clinical patient data informed the design of 3-D printed moulds to fabricate prostate targets. Tissue-mimicking materials were included that had the sonographic characteristics of the prostate and overlying tissues, as well as the clinically relevant physical response, to provide haptic feedback to the user. Through an iterative design process, prototypes were constructed. These prototypes were quantitatively evaluated using a specification list and evaluated by an experienced clinical brachytherapy oncologist; their feedback was implemented, and the results of this evaluation are presented.     

前列腺癌近距离治疗术后粒子移位状况分析

目的探讨使用^125I粒子进行前列腺癌近距离治疗后粒子移位的发生情况及影响因素。方法2003年12月至2008年10月共196例T1～T2期前列腺癌患者接受近距离治疗，累计植入粒子11 995粒，所有患者术后当天接受骨盆正位X线检查，术后1个月接受盆腔CT检查，3个月至半年后重复腹盆腔CT及胸片检查，将检查结果使用ITPS3．2软件分析，测算靶器官放射性剂量实际分布情况。记录粒子移位部位、前列腺体积、粒子植入数量、穿刺点数量、肿瘤Gleason评分、肿瘤分期等因素。结果21例患者出现粒子移位（10．7％，21／196），其中18例患者出现单个粒子移位，3例患者出现2枚粒子移位。移位粒子数共24粒（0．2％，24／11995），其中肺部移位粒子6粒，粒子移位至皮下或耻骨后其他区域16粒，排出体外2粒。结论前列腺体积、粒子植入总数量及前列腺包膜外粒子分布数量与粒子移位发生率具有相关性。发生粒子移位后局部靶器官治疗剂量不受影响，粒子移位无严重并发症产生。     

TRTE结合PSI在前列腺癌诊断中的应用价值研究

目的 研究经直肠实时组织弹性成像(TRTE)、定量参数峰值应变指数(PSI)在前列腺癌(PCa)诊断中的应用价值。方法 回顾性分析本院100例疑似PCa患者临床资料,所有患者均接受经直肠超声(TRUS)和TRTE超声检查,记录患者TRUS和TRTE影像特点。以穿刺活检结果为金标准,比较两种检查方法的准确性。计算PSI值,分析PSI判断前列腺病灶性质的准确性。结果 病理活检结果显示PCa 84例,前列腺良性病灶16例。TRUS和TRTE与病理结果均具有较好的一致性(Kappa = 0.612,0.797;P均 = 0.000)。TRUS和TRTE诊断PCa的灵敏度、特异度及准确度比较,差异均无统计学意义(P > 0.05)。PCa病变TRTE表现为病灶处呈局部蓝色或被蓝色覆盖,PSI判断前列腺病灶性质的AUC为0.854(95%CL = 0.735-0.973,S.E. = 0.061,P = 0.000),灵敏度为0.813,特异度为0.786,最佳截断值为11.75。PSI诊断PCa的灵敏度显著高于TRUS检查方法,差异有统计学意义(P ＜ 0.05)。结论 TRTE结合PSI定量参数诊断PCa准确性高,有助于提高阳性检出率。     

Comparison of photoacoustic imaging and histopathological examination in determining the dimensions of 52 human melanomas and nevi ex vivo

Surgical excision followed by histopathological examination is the gold standard for the diagnosis and staging of melanoma. Reoperations and unnecessary removal of healthy tissue could be reduced if non-invasive imaging techniques were available for presurgical tumor delineation. However, no technique has gained widespread clinical use to date due to shallow imaging depth or the absence of functional imaging capability. Photoacoustic (PA) imaging is a novel technology that combines the strengths of optical and ultrasound imaging to reveal the molecular composition of tissue at high resolution. Encouraging results have been obtained from previous animal and human studies on melanoma, but there is still a lack of clinical data. This is the largest study of its kind to date, including 52 melanomas and nevi. 3D multiwavelength PA scanning was performed ex vivo, using 59 excitation wavelengths from 680 nm to 970 nm. Spectral unmixing over this broad wavelength range, accounting for the absorption of several tissue chromophores, provided excellent contrast between healthy tissue and tumor. Combining the results of spectral analysis with spatially resolved information provided a map of the tumor borders in greater detail than previously reported. The tumor dimensions determined with PA imaging were strongly correlated with those determined by histopathological examination for both melanomas and nevi.     

Contrast‐Enhanced Transrectal Ultrasound for Follow‐up After Focal HIFU Ablation for Prostate Cancer

The optimal strategy for imaging after focal therapy for prostate cancer is evolving. This series is an initial report on the use of contrast‐enhanced transrectal ultrasound (TRUS) in follow‐up of patients after high‐intensity focused ultrasound (HIFU) hemiablation for prostate cancer. In 7 patients who underwent HIFU hemiablation, contrast‐enhanced TRUS findings were as follows: (1) contrast‐enhanced TRUS clearly showed the HIFU ablation defect as a sharply marginated nonenhancing zone in all patients; (2) contrast‐enhanced TRUS identified suspicious foci of recurrent enhancement within the ablation zone in 2 patients, facilitating image‐guided prostate biopsy, which showed prostate cancer; and (3) contrast‐enhanced TRUS findings correlated with multiparametric magnetic resonance imaging and biopsy histologic findings.     

Prostate segmentation in transrectal ultrasound using magnetic resonance imaging priors

Purpose

In the current standard of care, real-time transrectal ultrasound (TRUS) is commonly used for prostate brachytherapy guidance. As TRUS provides limited soft tissue contrast, segmenting the prostate gland in TRUS images is often challenging and subject to inter-observer and intra-observer variability, especially at the base and apex where the gland boundary is hard to define. Magnetic resonance imaging (MRI) has higher soft tissue contrast allowing the prostate to be contoured easily. In this paper, we aim to show that prostate segmentation in TRUS images informed by MRI priors can improve on prostate segmentation that relies only on TRUS images.

Methods

First, we compare the TRUS-based prostate segmentation used in the treatment of 598 patients with a high-quality MRI prostate atlas and observe inconsistencies at the apex and base. Second, motivated by this finding, we propose an alternative TRUS segmentation technique that is fully automatic and uses MRI priors. The algorithm uses a convolutional neural network to segment the prostate in TRUS images at mid-gland, where the gland boundary can be clearly seen. It then reconstructs the gland boundary at the apex and base with the aid of a statistical shape model built from an MRI atlas of 78 patients.

Results

Compared to the clinical TRUS segmentation, our method achieves similar mid-gland segmentation results in the 598-patient database. For the seven patients who had both TRUS and MRI, our method achieved more accurate segmentation of the base and apex with the MRI segmentation used as ground truth.

Conclusion

Our results suggest that utilizing MRI priors in TRUS prostate segmentation could potentially improve the performance at base and apex.

     

Simultaneous assessment of red blood cell aggregation and oxygen saturation under pulsatile flow using high-frequency photoacoustics

We investigate the feasibility of photoacoustic (PA) imaging for assessing the correlation between red blood cell (RBC) aggregation and the oxygen saturation (sO₂) in a simulated pulsatile blood flow system. For the 750 and 850 nm illuminations, the PA amplitude (PAA) increased and decreased as the mean blood flow velocity decreased and increased, respectively, at all beat rates (60, 120 and 180 bpm). The sO₂ also cyclically varied, in phase with the PAA for all beat rates. However, the linear correlation between the sO₂ and the PAA at 850 nm was stronger than that at 750 nm. These results suggest that the sO₂ can be correlated with RBC aggregation induced by decreased mean shear rate in pulsatile flow, and that the correlation is dependent on the optical wavelength. The hemodynamic properties of blood flow assessed by PA imaging may be used to provide a new biomarker for simultaneous monitoring blood viscosity related to RBC aggregation, oxygen delivery related to the sO₂ and their clinical correlation.OCIS codes: (110.5125) Photoacoustics, (170.1470) Blood or tissue constituent monitoring     

Towards ultrasound probe positioning optimization during prostate needle biopsy using pressure feedback

Purpose

Accurate Transrectal Ultrasound (TRUS)-guided prostate needle biopsy requires registering preoperative 3D TRUS or MR image, in which tumors and other suspicious areas are visible, to intraoperative 2D TRUS images. Such image registration is time-consuming while its real-time implementation is yet to be developed. To bypass this registration step, robotic needle biopsy systems can be used to place the US probe at the same position relative to the prostate during the 3D and 2D image acquisition to ensure similar prostate deformation. To have such similar deformation, only visual feedback is not sufficient as such feedback can be used to only guarantee that the whole prostate is within the field of view irrespective of the probe’s orientation. As such, contact pressure feedback can be utilized to ensure consistent minimum contact between the probe and prostate.

Method

A robotic system is proposed where a TRUS probe with pressure sensor array is used. The contact pressure can be measured during imaging and used to provide feedback in conjunction with an optimization algorithm for consistent probe positioning. The robotic system is driven by the feedback to position the probe such that pressure pattern of the sensors during 2D image acquisition is similar to the pressure pattern during 3D image acquisition. The proposed method takes into account the patient’s body movement expected during image acquisition. In this study, an in silico phantom is used where the simulated contact pressure distribution required in the optimization algorithm is obtained using a prostate finite element model.

Result

Starting from an arbitrary position where the probe contacts the phantom, this position was varied systematically until a position corresponding to maximum pressure pattern similarity between contact pressure patterns corresponding to the 2D and 3D imaging was achieved successfully.

Conclusion

Results obtained from the in silico phantom study indicate that the proposed technique is capable of ensuring having only minimal relative prostate deformation between preoperative image acquisition and intraoperative imaging used for guiding needle biopsy, paving the way for faster and more accurate registration.     

Benefits of pre‐biopsy multi‐parametric magnetic resonance imaging scanning in the initial assessment of prostate cancer

Traditionally, men referred for investigation of raised prostate specific antigen (PSA) could expect to be investigated via blind TRUS biopsy. In recent years, the availability of pre‐biopsy imaging with multi‐parametric magnetic resonance imaging (mp‐MRI) has allowed urology centres to improve their triage and care of this patient cohort. The ability to identify discrete lesions for more accurately targeted TRUS, stream patients with anterior lesions for trans‐perineal biopsy, and of course to prevent those with no evidence of clinically significant prostate cancer from being subjected to unnecessary procedures has proved pre‐biopsy mp‐MRI a valuable tool in the assessment and diagnosis of prostate cancer. Our service recently audited the impact of the introduction of mp‐MRI on our prostate cancer assessment pathway. An analysis of the outcomes of 1558 referrals over a 2‐year period, and found that pre‐biopsy imaging has resulted in a marked reduction in unnecessary procedures and more accurate targeting of lesions, leading to improved outcomes for patients.     

Tissue-mimicking phantoms for photoacoustic and ultrasonic imaging

In both photoacoustic (PA) and ultrasonic (US) imaging, overall image quality is influenced by the optical and acoustical properties of the medium. Consequently, with the increased use of combined PA and US (PAUS) imaging in preclinical and clinical applications, the ability to provide phantoms that are capable of mimicking desired properties of soft tissues is critical. To this end, gelatin-based phantoms were constructed with various additives to provide realistic acoustic and optical properties. Forty-micron, spherical silica particles were used to induce acoustic scattering, Intralipid(?) 20% IV fat emulsion was employed to enhance optical scattering and ultrasonic attenuation, while India Ink, Direct Red 81, and Evans blue dyes were utilized to achieve optical absorption typical of soft tissues. The following parameters were then measured in each phantom formulation: speed of sound, acoustic attenuation (from 6 to 22 MHz), acoustic backscatter coefficient (from 6 to 22 MHz), optical absorption (from 400 nm to 1300 nm), and optical scattering (from 400 nm to 1300 nm). Results from these measurements were then compared to similar measurements, which are offered by the literature, for various soft tissue types. Based on these comparisons, it was shown that a reasonably accurate tissue-mimicking phantom could be constructed using a gelatin base with the aforementioned additives. Thus, it is possible to construct a phantom that mimics specific tissue acoustical and/or optical properties for the purpose of PAUS imaging studies.     

Red emissive AIE nanodots with high two-photon absorption efficiency at 1040 nm for deep-tissue in vivo imaging

Deep-tissue penetration is highly required in in vivo optical bioimaging. We synthesized a type of red emissive fluorophore BT with aggregation-induced emission (AIE) property. BT molecules were then encapsulated with amphiphilic polymers to form nanodots, and a large two-photon absorption (2PA) cross-section of 2.9 × 10⁶ GM at 1040 nm was observed from each BT nanodot, which was much larger than those at the wavelengths of 770 to 860 nm. In addition, 1040 nm light was found to have better penetration and focusing capability than 800 nm light in biological tissue, according to the Monte Carlo simulation. The toxicity and tissue distribution of BT nanodots were studied, and they were found to have good biocompatibility. BT nanodots were then utilized for in vivo imaging of mouse ear and brain, and an imaging depth of 700 μm was obtained with the femtosecond (fs) excitation of 1040 nm. The red emissive AIE nanodots with high 2PA efficiency at 1040 nm would be useful for deep-tissue functional bioimaging in the future.OCIS codes: (160.2540) Fluorescent and luminescent materials, (160.4236) Nanomaterials, (170.3880) Medical and biological imaging, (180.2520) Fluorescence microscopy, (180.4315) Nonlinear microscopy, (190.4180) Multiphoton processes     

Quantitative comparison of the OCT imaging depth at 1300 nm and 1600 nm

One of the present challenges in optical coherence tomography (OCT) is the visualization of deeper structural morphology in biological tissues. Owing to a reduced scattering, a larger imaging depth can be achieved by using longer wavelengths. In this work, we analyze the OCT imaging depth at wavelengths around 1300 nm and 1600 nm by comparing the scattering coefficient and OCT imaging depth for a range of Intralipid concentrations at constant water content. We observe an enhanced OCT imaging depth for 1600 nm compared to 1300 nm for Intralipid concentrations larger than 4 vol.%. For higher Intralipid concentrations, the imaging depth enhancement reaches 30%. The ratio of scattering coefficients at the two wavelengths is constant over a large range of scattering coefficients and corresponds to a scattering power of 2.8 ± 0.1. Based on our results we expect for biological tissues an increase of the OCT imaging depth at 1600 nm compared to 1300 nm for samples with high scattering power and low water content.     

Comparison of transrectal ultrasound prostatic volume estimation with magnetic resonance imaging volume estimation and surgical specimen weight in patients with benign prostatic hyperplasia

There are relatively few reports in the literature comparing transrectal ultrasound (TRUS) to magnetic resonance imaging (MRI) in estimating the volume of the prostate in the management of benign prostatic hyperplasia (BPH). In this study, we compared volumes determined by TRUS with MRI and TRUS-estimated weights with surgical specimen weights. The main findings of this study were (a) TRUS and MRI measurement of prostate volumes are quite similar; and (b) TRUS underestimates (by 10%) the prostatic weight as determined from the surgical specimens. A better volume estimate can thus be obtained by multiplying the TRUS measurement by a factor of 1.10. We conclude that because TRUS is cheap, user-friendly, noninvasive, and equally as accurate as MRI, it should be the preferred modality in the follow-up of BPH patients. © 1996 John Wiley & Sons, Inc.